chr5-146469579-A-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_001382548.1(TCERG1):c.1234A>G(p.Met412Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000943 in 1,612,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000099 ( 0 hom. )
Consequence
TCERG1
NM_001382548.1 missense
NM_001382548.1 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 7.15
Genes affected
TCERG1 (HGNC:15630): (transcription elongation regulator 1) This gene encodes a nuclear protein that regulates transcriptional elongation and pre-mRNA splicing. The encoded protein interacts with the hyperphosphorylated C-terminal domain of RNA polymerase II via multiple FF domains, and with the pre-mRNA splicing factor SF1 via a WW domain. Alternative splicing results in multiple transcripts variants encoding different isoforms. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, TCERG1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.07311922).
BS2
?
High AC in GnomAd at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCERG1 | NM_001382548.1 | c.1234A>G | p.Met412Val | missense_variant | 7/23 | ENST00000679501.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCERG1 | ENST00000679501.2 | c.1234A>G | p.Met412Val | missense_variant | 7/23 | NM_001382548.1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152218Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000922 AC: 23AN: 249478Hom.: 0 AF XY: 0.000141 AC XY: 19AN XY: 135166
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GnomAD4 exome AF: 0.0000986 AC: 144AN: 1460094Hom.: 0 Cov.: 30 AF XY: 0.000116 AC XY: 84AN XY: 726382
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GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152336Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5AN XY: 74502
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 24, 2022 | The c.1234A>G (p.M412V) alteration is located in exon 7 (coding exon 7) of the TCERG1 gene. This alteration results from a A to G substitution at nucleotide position 1234, causing the methionine (M) at amino acid position 412 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
Gain of sheet (P = 0.0344);.;
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at